Association of genetic variants in enamel-formation genes with dental caries: A meta- and gene-cluster analysis

Previous studies have reported the association between multiple genetic variants in the enamel-formation genes and the risk of dental caries with inconsistent results. We performed a systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases for studies published before March 21, 2020 and conducted meta-, gene-based and gene-cluster analysis on the association between genetic variants in the enamel-formation genes and the risk of dental caries. We identified 21 relevant publications including a total of 24 studies for analysis. The genetic variant rs17878486 in AMELX was significantly associated with dental caries risk (OR = 1.40, 95% CI: 1.02–1.93, P = 0.037). We found no significant association between the risk of dental caries with rs12640848 in ENAM (OR = 1.15, 95% CI: 0.88–1.52, P = 0.310), rs1784418 in MMP20 (OR = 1.07, 95% CI: 0.76–1.49, P = 0.702) and rs3796704 in ENAM (OR = 1.06, 95% CI: 0.96–1.17, P = 0.228). Gene-based analysis indicated that multiple genetic variants in AMELX showed joint association with the risk of dental caries (6 variants; P < 10⁻⁵), so did genetic variants in MMP13 (3 variants; P = 0.004), MMP2 (3 variants; P < 10⁻⁵), MMP20 (2 variants; P < 10⁻⁵) and MMP3 (2 variants; P < 10⁻⁵). The gene-cluster analysis indicated a significant association between the genetic variants in this enamel-formation gene cluster and the risk of dental caries (P < 10⁻⁵). The present meta-analysis revealed that genetic variant rs17878486 in AMELX was associated with dental caries, and multiple genetic variants in the enamel-formation genes jointly contributed to the risk of dental caries, supporting the role of genetic variants in the enamel-formation genes in the etiology of dental caries.     

LncRNA PDCD4-AS1 alleviates triple negative breast cancer by increasing expression of IQGAP2 via miR-10b-5p

ObjectiveMounting evidence demonstrates that long non-coding RNA (lncRNA) is dysregulated in breast cancers. This study was designed to detect the influences and regulatory mechanism of lncRNA PDCD4-AS1 in triple-negative breast cancer (TNBC).MethodsqRT-PCR and Western blot were utilized to investigate the expression levels of PDCD4-AS1, miR-10b-5p and IQGAP2 in TNBC tissues and cells. Online software and luciferase reporter gene system were employed to testify the interactions among these molecules. Loss and gain of function of PDCD4-AS1, miR-10b-5p or IQGAP2 were performed before MTT and colony formation assay, TUNEL staining in addition to Transwell and scratch assays were applied to measure the cell biological functions.ResultsIn this work, PDCD4-AS1 and IQGAP2 were lowly expressed while miR-10b-5p was strongly expressed in TNBC tissues and cells. PDCD4-AS1 or IQGAP2 overexpression effectively attenuated TNBC cell proliferation, migration and invasion, and increased the apoptosis rate, while this effect was abandoned in response to miR-10b-5p mimics transfection. miR-10b-5p bound to IQGAP2 and acted as a downstream target of PDCD4-AS1.ConclusionOur findings identified lncRNA PDCD4-AS1 as a tumor suppressor in TNBC by regulating IQGAP2 expression via miR-10b-5p, giving a novel insight into the regulatory mechanism of PDCD4-AS1 in the pathogenesis of TNBC.     

Expression characterization and activity analysis of a cathepsin B from Pacific abalone Haliotis discus hannai

Cathepsin B (EC 3.4.22.1) is a member of lysosomal cysteine protease and has a papain-like fold. In mammals, it is involved in protein degradation and other physiological processes including immune response. However, little is known about the function of cathepsin B in mollusks. In this study, we identified and analyzed a cathepsin B homolog (HdCatB) from Pacific abalone (Haliotis discus hannai), an economically important mollusk species cultured in East Asia. HdCatB is composed of 336 amino acid residues and its mature form is predicted to start at residue 86. HdCatB possesses typical domain architecture of cathepsin B and contains a propeptide region and a cysteine protease domain, the latter containing the four active site residues (Q108, C114, H282, and N302) that are conserved in many different organisms. HdCatB shares 40–60% overall sequence identities with the cathepsin Bofa number of vertebrates and invertebrates and is phylogenetically very close to mollusk cathepsin B. Quantitative real time RT-PCR analysis revealed that HdCatB expression occurred in multiple tissues and was upregulated by bacterial infection. Recombinant HdCatB purified from Escherichia coli exhibited apparent protease activity, which was optimal at 45 °C and pH 6.0. These results indicate that HdCatB is a bioactive protease that is likely to be implicated in the immune response of abalone during bacterial infection.     

Cloning and expression analysis of a CMS-related gene BcCoi1 from Brassica campestris ssp. chinensis

BcCoi1, a cytoplasmic male sterility related gene, which was isolated from flower buds of Brassica campestris ssp. chinensis Makino using the RACE technology, was characterized and submitted to the NCBI GenBank (accession no. GU263836). The gene encodes a 67.78-kD protein containing 16 leucine-rich repeats and an N-terminal F-box motif and is extremely similar to Arabidopsis thaliana Coi1 gene. The Southern blot showed that BcCoi1 belongs to a multigene family. In A. thaliana, the Coi1 gene is involved in jasmonate signaling, and Coi1 mutant displayed male sterility. In this study, qPCR results demonstrated that BcCoi1 was accumulated in stamens and was significantly higher expressed in flower organs of the maintainer line than in the CMS one. At the microsporocyte development stage, the gene was expressed at a significantly lower extent in the CMS line than in the maintainer line. This expression profile presumes that BcCoi1 plays a role in early microspore development in non-heading Chinese cabbage.     

Temperature-related effects of treatments with jasmonic and salicylic acids on Arabidopsis infected with cucumber mosaic virus

Plant-virus interactions are affected by environmental factors, including temperature. Plant defenses are often inhibited by high or low temperature. In this study, oxidative damage and gene expression were detected in Arabidopsis thaliana infected with cucumber mosaic virus (CMV) at different temperatures. Before virus inoculation, plants were treated with jasmonic acid (JA) and salicylic acid (SA), both of which are important signaling molecules in plant defense responses. The levels of MDA and hydrogen peroxide (H₂O₂), and electrolyte leakage were significantly higher in CMV-infected leaves at 15 and 37°C. The accumulation of H₂O₂ and superoxide radical (O ₂ ^·? ) was obviously suppressed by spraying with JA followed by SA (JA → SA) at different temperatures. The CMV-CP expression analysis showed that virus replication was inhibited efficiently in the (JA → SA) treatment. Therefore, many JA- and SA-responsible resistance genes were quantified; MPK4 was expressed highly and steadily in the (JA → SA) treatment. To further confirm the role of MPK4, the CMV-CP gene expression was evaluated in wild-type Arabidopsis and its mpk4 mutant infected with CMV. The results suggested that MPK4 might play an important role in the antagonism between JA and SA at temperature fluctuation.     

HCV-specific interleukin-21+CD4+ T cells responses associated with viral control through the modulation of HCV-specific CD8+ T cells function in chronic hepatitis C patients

Interleukin-21 (IL-21)+CD4+ T cells are involved in the immune response against hepatitis B virus (HBV) by secreting IL-21. However, the role of IL-21+CD4+ T cells in the immune response against chronic hepatitis C (CHC) virus infection is poorly understood. This study aimed to investigate the role of IL-21+CD4+ T cells in CHC patients and the potential mechanisms. The study subjects included nineteen CHC patients who were grouped by viral load (low, < 10⁶ RNA copies/ml, n = 8; high, > 10⁶ RNA copies/ml, n = 11). The peripheral frequency of HCV-specific IL-21+CD4+ T cells was higher in the low viral load group and was negatively correlated with the serum HCV RNA viral load in all CHC patients. Meanwhile, IL-21+ cells accumulated in the liver in the low viral load group. In vitro, IL-21 treatment increased the expression of proliferation markers and cytolytic molecules on HCV-specific CD8+ T cells. In summary, these findings suggest that HCV-specific IL-21+CD4+ T cells might contribute to HCV control by rescuing HCV-specific CD8+ T cells in CHC patients.     

Differential requirement of Oryza sativa RAR1 in immune receptor-mediated resistance of rice to Magnaporthe oryzae

The required for Mla12 resistance (RAR1) protein is essential for the plant immune response. In rice, a model monocot species, the function of Oryza sativa RAR1 (OsRAR1) has been little explored. In our current study, we characterized the response of a rice osrar1 T-DNA insertion mutant to infection by Magnaporthe oryzae, the causal agent of rice blast disease. osrar1 mutants displayed reduced resistance compared with wild type rice when inoculated with the normally virulent M. oryzae isolate PO6-6, indicating that OsRAR1 is required for an immune response to this pathogen. We also investigated the function of OsRAR1 in the resistance mechanism mediated by the immune receptor genes Pib and Pi5 that encode nucleotide binding-leucine rich repeat (NB-LRR) proteins. We inoculated progeny from Pib/osrar1 and Pi5/osrar1 heterozygous plants with the avirulent M. oryzae isolates, race 007 and PO6-6, respectively. We found that only Pib-mediated resistance was compromised by the osrar1 mutation and that the introduction of the OsRAR1 cDNA into Pib/osrar1 rescued Pib-mediated resistance. These results indicate that OsRAR1 is required for Pib-mediated resistance but not Pi5-mediated resistance to M. oryzae.